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. 1995 Jan 1;181(1):105–113. doi: 10.1084/jem.181.1.105

Loss of surface immunoglobulin expression precedes B cell death by apoptosis in the bursa of Fabricius

PMCID: PMC2191850  PMID: 7806997

Abstract

The vast majority of lymphocytes generated daily in the chicken bursa of Fabricius do not emigrate to the periphery but die in situ. Apoptotic cells in the bursa can be readily detected by the presence of fragmented DNA and by the large numbers of condensed cellular nuclei observed by electron microscopy. Consequently, most newly generated lymphocytes die by programmed cell death. We show that bursal cells divide rapidly and apoptotic cells are derived from rapidly dividing precursors. Analysis of the phenotype of bursal cells undergoing apoptosis demonstrated that cell death does not occur in the most mature bursal cell population and is therefore not random. High levels of surface Ig are expressed on bursal cells entering S phase of the cell cycle. In contrast, bursal cells in the early stages of apoptosis in vivo express very low to undetectable levels of surface Ig but were unequivocally confirmed as being of the B lineage by polymerase chain reaction (PCR) detection of rearranged Ig genes. Bursal cells induced to undergo apoptosis in vitro express high levels of surface Ig demonstrating that induction of apoptosis does not in itself induce a loss of surface Ig expression. Consequently, loss of surface Ig expression precedes bursal cell death by apoptosis in vivo, suggesting that maintenance of a threshold level of surface Ig may be a requirement for the continued progression of chicken B lymphocyte development in the bursa.

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Selected References

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  1. Benatar T., Iacampo S., Tkalec L., Ratcliffe M. J. Expression of immunoglobulin genes in the avian embryo bone marrow revealed by retroviral transformation. Eur J Immunol. 1991 Oct;21(10):2529–2536. doi: 10.1002/eji.1830211033. [DOI] [PubMed] [Google Scholar]
  2. Benatar T., Tkalec L., Ratcliffe M. J. Stochastic rearrangement of immunoglobulin variable-region genes in chicken B-cell development. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7615–7619. doi: 10.1073/pnas.89.16.7615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boehme S. A., Lenardo M. J. Propriocidal apoptosis of mature T lymphocytes occurs at S phase of the cell cycle. Eur J Immunol. 1993 Jul;23(7):1552–1560. doi: 10.1002/eji.1830230724. [DOI] [PubMed] [Google Scholar]
  4. Bosma M. J., Carroll A. M. The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol. 1991;9:323–350. doi: 10.1146/annurev.iy.09.040191.001543. [DOI] [PubMed] [Google Scholar]
  5. Buerstedde J. M., Reynaud C. A., Humphries E. H., Olson W., Ewert D. L., Weill J. C. Light chain gene conversion continues at high rate in an ALV-induced cell line. EMBO J. 1990 Mar;9(3):921–927. doi: 10.1002/j.1460-2075.1990.tb08190.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carlson L. M., Oettinger M. A., Schatz D. G., Masteller E. L., Hurley E. A., McCormack W. T., Baltimore D., Thompson C. B. Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene conversion. Cell. 1991 Jan 11;64(1):201–208. doi: 10.1016/0092-8674(91)90221-j. [DOI] [PubMed] [Google Scholar]
  7. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992;10:267–293. doi: 10.1146/annurev.iy.10.040192.001411. [DOI] [PubMed] [Google Scholar]
  8. Golstein P., Ojcius D. M., Young J. D. Cell death mechanisms and the immune system. Immunol Rev. 1991 Jun;121:29–65. doi: 10.1111/j.1600-065x.1991.tb00822.x. [DOI] [PubMed] [Google Scholar]
  9. Hartley S. B., Crosbie J., Brink R., Kantor A. B., Basten A., Goodnow C. C. Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature. 1991 Oct 24;353(6346):765–769. doi: 10.1038/353765a0. [DOI] [PubMed] [Google Scholar]
  10. Houssaint E., Diez E., Pink J. R. Ontogeny and tissue distribution of the chicken Bu-1a antigen. Immunology. 1987 Nov;62(3):463–470. [PMC free article] [PubMed] [Google Scholar]
  11. Houssaint E., Mansikka A., Vainio O. Early separation of B and T lymphocyte precursors in chick embryo. J Exp Med. 1991 Aug 1;174(2):397–406. doi: 10.1084/jem.174.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jacob J., Kelsoe G., Rajewsky K., Weiss U. Intraclonal generation of antibody mutants in germinal centres. Nature. 1991 Dec 5;354(6352):389–392. doi: 10.1038/354389a0. [DOI] [PubMed] [Google Scholar]
  13. Jacobsen K., Osmond D. G. Microenvironmental organization and stromal cell associations of B lymphocyte precursor cells in mouse bone marrow. Eur J Immunol. 1990 Nov;20(11):2395–2404. doi: 10.1002/eji.1830201106. [DOI] [PubMed] [Google Scholar]
  14. Jenkinson E. J., Kingston R., Smith C. A., Williams G. T., Owen J. J. Antigen-induced apoptosis in developing T cells: a mechanism for negative selection of the T cell receptor repertoire. Eur J Immunol. 1989 Nov;19(11):2175–2177. doi: 10.1002/eji.1830191132. [DOI] [PubMed] [Google Scholar]
  15. Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991 Apr 4;350(6317):423–426. doi: 10.1038/350423a0. [DOI] [PubMed] [Google Scholar]
  16. Lassila O. Emigration of B cells from chicken bursa of Fabricius. Eur J Immunol. 1989 May;19(5):955–958. doi: 10.1002/eji.1830190527. [DOI] [PubMed] [Google Scholar]
  17. Lassila O., Lefkovits I., Alanen A. Immunoglobulin diversification in bursal duct-ligated chickens. Eur J Immunol. 1989 Jul;19(7):1343–1345. doi: 10.1002/eji.1830190730. [DOI] [PubMed] [Google Scholar]
  18. Liu Y. J., Joshua D. E., Williams G. T., Smith C. A., Gordon J., MacLennan I. C. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. doi: 10.1038/342929a0. [DOI] [PubMed] [Google Scholar]
  19. Lydyard P. M., Grossi C. E., Cooper M. D. Ontogeny of B cells in the chicken. I. Sequential development of clonal diversity in the bursa. J Exp Med. 1976 Jul 1;144(1):79–97. doi: 10.1084/jem.144.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mansikka A., Sandberg M., Lassila O., Toivanen P. Rearrangement of immunoglobulin light chain genes in the chicken occurs prior to colonization of the embryonic bursa of Fabricius. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9416–9420. doi: 10.1073/pnas.87.23.9416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McCormack W. T., Tjoelker L. W., Barth C. F., Carlson L. M., Petryniak B., Humphries E. H., Thompson C. B. Selection for B cells with productive IgL gene rearrangements occurs in the bursa of Fabricius during chicken embryonic development. Genes Dev. 1989 Jun;3(6):838–847. doi: 10.1101/gad.3.6.838. [DOI] [PubMed] [Google Scholar]
  22. Motyka B., Reynolds J. D. Apoptosis is associated with the extensive B cell death in the sheep ileal Peyer's patch and the chicken bursa of Fabricius: a possible role in B cell selection. Eur J Immunol. 1991 Aug;21(8):1951–1958. doi: 10.1002/eji.1830210825. [DOI] [PubMed] [Google Scholar]
  23. Neiman P. E., Thomas S. J., Loring G. Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5857–5861. doi: 10.1073/pnas.88.13.5857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nemazee D. A., Bürki K. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature. 1989 Feb 9;337(6207):562–566. doi: 10.1038/337562a0. [DOI] [PubMed] [Google Scholar]
  25. Osmond D. G., Kim N., Manoukian R., Phillips R. A., Rico-Vargas S. A., Jacobsen K. Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of scid mice. Blood. 1992 Apr 1;79(7):1695–1703. [PubMed] [Google Scholar]
  26. Paramithiotis E., Ratcliffe M. J. B cell emigration directly from the cortex of lymphoid follicles in the bursa of Fabricius. Eur J Immunol. 1994 Feb;24(2):458–463. doi: 10.1002/eji.1830240229. [DOI] [PubMed] [Google Scholar]
  27. Paramithiotis E., Ratcliffe M. J. Bursa-dependent subpopulations of peripheral B lymphocytes in chicken blood. Eur J Immunol. 1993 Jan;23(1):96–102. doi: 10.1002/eji.1830230116. [DOI] [PubMed] [Google Scholar]
  28. Ratcliffe M. J., Ivanyi J. Allotype suppression in the chicken. IV. Deletion of B cells and lack of suppressor cells during chronic suppression. Eur J Immunol. 1981 Apr;11(4):306–310. doi: 10.1002/eji.1830110408. [DOI] [PubMed] [Google Scholar]
  29. Ratcliffe M. J. Ligation of cell surface immunoglobulin in the chicken bursa of Fabricius. Res Immunol. 1993 Jul-Sep;144(6-7):450–455. doi: 10.1016/0923-2494(93)80131-h. [DOI] [PubMed] [Google Scholar]
  30. Ratcliffe M. J., Tkalec L. Cross-linking of the surface immunoglobulin on lymphocytes from the bursa of Fabricius results in second messenger generation. Eur J Immunol. 1990 May;20(5):1073–1078. doi: 10.1002/eji.1830200519. [DOI] [PubMed] [Google Scholar]
  31. Reynaud C. A., Anquez V., Grimal H., Weill J. C. A hyperconversion mechanism generates the chicken light chain preimmune repertoire. Cell. 1987 Feb 13;48(3):379–388. doi: 10.1016/0092-8674(87)90189-9. [DOI] [PubMed] [Google Scholar]
  32. Reynaud C. A., Dahan A., Anquez V., Weill J. C. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region. Cell. 1989 Oct 6;59(1):171–183. doi: 10.1016/0092-8674(89)90879-9. [DOI] [PubMed] [Google Scholar]
  33. Reynaud C. A., Imhof B. A., Anquez V., Weill J. C. Emergence of committed B lymphoid progenitors in the developing chicken embryo. EMBO J. 1992 Dec;11(12):4349–4358. doi: 10.1002/j.1460-2075.1992.tb05534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reynolds J. D. Mitotic rate maturation in the Peyer's patches of fetal sheep and in the bursa of Fabricius of the chick embryo. Eur J Immunol. 1987 Apr;17(4):503–507. doi: 10.1002/eji.1830170411. [DOI] [PubMed] [Google Scholar]
  35. Rolink A., Melchers F. Molecular and cellular origins of B lymphocyte diversity. Cell. 1991 Sep 20;66(6):1081–1094. doi: 10.1016/0092-8674(91)90032-t. [DOI] [PubMed] [Google Scholar]
  36. Veromaa T., Vainio O., Eerola E., Toivanen P. Monoclonal antibodies against chicken Bu-1a and Bu-1b alloantigens. Hybridoma. 1988 Feb;7(1):41–48. doi: 10.1089/hyb.1988.7.41. [DOI] [PubMed] [Google Scholar]
  37. Weill J. C., Reynaud C. A. The chicken B cell compartment. Science. 1987 Nov 20;238(4830):1094–1098. doi: 10.1126/science.3317827. [DOI] [PubMed] [Google Scholar]
  38. Yelton D. E., Desaymard C., Scharff M. D. Use of monoclonal anti-mouse immunoglobulin to detect mouse antibodies. Hybridoma. 1981;1(1):5–11. doi: 10.1089/hyb.1.1981.1.5. [DOI] [PubMed] [Google Scholar]

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